Grey wolf genomic history reveals a dual ancestry of dogs

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived1,2,3,4,5,6,7,8. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT88 40,000–30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located

Impact of Percutaneous Oestradiol Gels in Postmenopausal Hormone Replacement Therapy on Clinical Symptoms and Endometrium

OBJECTIVE: To compare the effects on endometrium, climacteric symptoms and the menstrual cycle, and the clinical and biological tolerance of two percutaneous oestradiol gels used as hormone replacement therapy. DESIGN: A large open randomised multicentre study. SETTING: France and Belgium. PARTICIPANTS: Two-hundred and fifty-four women with an intact uterus and who had experienced a natural menopause received either Oestrogel (n = 126) or Estreva, a new formulation of oestradiol gel (n = 128), (1.5 mg of oestradiol/day) for the 24 first days of each calendar month during six consecutive months. Nomegestrol acetate (Lutenyl), a norprogesterone derivative, was administered (5 mg/day) from day 11 to day 24 of each oestradiol cycle. MAIN OUTCOME MEASURES: Examination of endometrial biopsies taken before treatment and between days 18 and 24 of the last treatment cycle, climacteric symptoms assessed using a modified Kupperman index, control of menstrual cycle evaluated by diary cards, and clinical and biological tolerance. RESULTS: Both treatments lowered the frequency and intensity of hot flushes and the global Kupperman index. 96% of the cycles were followed by withdrawal bleeding. Breakthrough bleeding or spotting resulted in premature discontinuation of treatment in one volunteer. Mastodynia occurred in 20 women and contributed to the premature termination of treatment in three of them. Endometrial biopsies taken at the end of treatment showed identical histologies in both groups, with a secretory pattern in the majority of women, and absence of hyperplasia. CONCLUSIONS: This trial confirmed that, when the two oestradiol gels tested were administered cyclically with nomegestrol acetate to postmenopausal women, they were well tolerated, effective and suitable for the treatment of oestrogen deficiency syndrome